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Hapten dyes (1904)

Karl Landsteiner was one of the giants in immunology with several profound discoveries to his credit – not least the discovery of blood groups, for which he earned a Nobel prize in 1930. However, he considered his research on antigen specificity, and in particular the discovery of a group of chemicals he called “haptens”, as one of his most profound pieces of work.

The name hapten comes from the Latin word meaning to “fasten” because when these small molecules bind to larger proteins they elicit an immune response – in other words they stimulate the production of antibodies. Haptens on their own do not stimulate an immune reaction, which means they are not immunogenic. Yet when “fastened” to a protein the entire complex becomes highly immunogenic.

Landsteiner covalently bonded the haptens, which were small aromatic amines, to some larger immunogenic proteins and produced aromatic amine-protein complexes. When injected into experimental animals these aromatic amine-protein complexes induced the formation of antibodies against the aromatic amines.

Landsteiner first discovered haptens in 1904 while working in Vienna but it was only between 1919 and 1922 that he published a series of scientific papers on his new haptens, along with other work related to the immune response. It was pioneering research into synthetic antigens that could stimulate an immune response – essential work in the understanding and development of vaccines.

The way the poison ivy attacks the skin is one of the best examples of a natural hapten. It produces a substance called urushiol which is absorbed through the skin when someone handles the plant and, once absorbed, the urushiol is oxidised in the skin cells to product the actual hapten, a reactive molecule called guinone. Guinone then reacts with skin proteins to create highly immunogenic antigens. Once initially exposed to poison ivy, the immune system reacts to the combination of hapten and protein, causing the skin typical blisters.